Biopsy, Histology, and Molecular Testing in Neuro-Oncology

In neuro-oncology, understanding the biology of a brain or spinal tumor is essential for selecting the most effective and individualized treatment plan. Diagnostic tools such as biopsy, histology, immunohistochemistry, and molecular testing are required to accurately classify tumors and guide personalized therapy for patients with brain tumors.

Biopsy and Surgical Tissue Sampling in Brain Tumors

A biopsy involves obtaining a small sample of tumor tissue for diagnostic evaluation. In some cases, brain tumor surgery is performed without a prior biopsy, particularly when imaging strongly suggests a resectable tumor and immediate removal is safe and beneficial. This approach is common for suspected gliomas, meningiomas, and brain metastases.

During these surgeries, tissue samples are collected intraoperatively and sent for detailed pathological and molecular analysis. When tumors are located in deep or high-risk areas of the brain, a stereotactic biopsy may be performed first to confirm the diagnosis before further treatment decisions are made.

Histological Analysis of Brain Tumors

Histology is the foundation of brain tumor diagnosis. Pathologists examine tumor tissue under a microscope to determine:

• Tumor type

• Tumor grade (low-grade vs. high-grade)

• Cellular structure, growth patterns, and invasiveness

Histological analysis helps differentiate between various tumor types, such as low-grade gliomas, high-grade gliomas (glioblastoma), meningiomas, and metastatic brain tumors, and provides important prognostic information.

Immunohistochemistry and Molecular Testing in Neuro-Oncology

Immunohistochemical and molecular testing provide deeper insight into the genetic and biological drivers of brain tumors. These tests identify specific mutations, protein expression patterns, and molecular alterations that directly influence prognosis and treatment selection.

Common examples include:

• IDH1/IDH2 mutations in gliomas, associated with better prognosis and treatment planning

• MGMT promoter methylation in glioblastoma, predicting response to chemotherapy such as temozolomide

• 1p/19q codeletion, which defines oligodendrogliomas that respond well to combined chemotherapy and radiation therapy

• BRAF V600E mutations, found in certain gliomas and gangliogliomas, allowing treatment with targeted BRAF inhibitors

• NF2 and other molecular alterations in meningiomas, supporting risk stratification and advanced treatment decisions

These molecular markers are essential for selecting targeted therapies, immunotherapies, and personalized treatment strategies.

Comprehensive Genomic Profiling

In selected patients, comprehensive genomic profiling such as FoundationOne® testing may be performed on tumor tissue. FoundationOne® analyzes hundreds of cancer-related genes in a single test, identifying actionable genetic alterations that may guide:

• Targeted therapies

• Immunotherapy options

• Eligibility for clinical trials

This advanced testing is particularly valuable in aggressive, recurrent, or treatment-resistant brain tumors, where standard treatment options may be limited.

Personalized Treatment Planning in Neuro-Oncology

Together, biopsy or surgical tissue sampling, histology, immunohistochemistry, molecular testing, and comprehensive genomic profiling provide a complete understanding of a tumor’s biology. This integrated diagnostic approach allows neuro-oncology teams to:

• Accurately classify brain tumors

• Assess prognosis

• Design individualized, evidence-based treatment plans

By tailoring treatment to the specific molecular characteristics of each tumor, modern neuro-oncology aims to maximize treatment effectiveness while minimizing unnecessary therapies—ultimately improving outcomes and quality of life for patients.

The article was medically reviewed by the Neuro-Oncology Team
Last update: December 14, 2025
Neuro-oncology Institute, Barcelona.